Recently, besides conventional medicinal drugs containing a synthesized chemical substance as a main composition, medicinal drugs originated from biological materials produced by biotechnology, namely, biologics, have been increasingly used. Of the biologics, particularly remarkable biologics are cell products such as antibodies. These biologics have extremely high effects but expensiveness is a problem. Furthermore, since biologics are produced from organisms, there is possibility that variation in quality or the like during a production step is higher than that of conventional medicinal drugs. Accordingly, it has been required to develop a system for producing a product at low cost by culturing a large amount of cells at a time, and a culture system which can improve quality of a product by keeping a culture environment stable and maintaining quality of cells.
Moreover, in recent years, practical use of regenerative medicine using cells for therapy has begun. In Japan, some commercially available products, which have been approved by the pharmaceutical law, are presently used for the skin and cartilage tissue. As a therapy presently used, cells are partly taken from a patient, proliferated, and then formed into a tissue and transplanted. In the future, it is expected that a desired cell is induced from a somatic stem cell and a pluripotent stem cell and used in practical therapy. In realizing such a therapy, extremely a large amount of cells are required for preparing a sufficient size of tissue to be transplanted to a patient. According to estimation, cells in the order of 109 are required, for example, for the left ventricle of the heart. To prepare such a large amount of cultured cells by currently available techniques, a great deal of labor and cost is required.
In addition, most of the cell culture steps presently employed are manually operated. Because of this, operation mistake and a risk of e.g., bacterial contamination of a culture system cannot be completely avoided.
As mentioned above, it has been desired to realize an effective culture system for culturing cells with a further higher density at low cost in an automated way. As a culture system satisfying these requirements, various systems have been proposed including a system using semipermeable membrane based on dialysis principle, in which cells are cultured while cleansing a culture fluid in a continuous manner (for example, see Patent Literatures 1 and 2).
However, if cells are cultured in these systems, pressure difference between outside and inside semipermeable membrane and concentration gradient of compositions are produced by perfusion of a culture fluid, with the result that the solvent of a culture fluid moves across the membrane. If a culture is carried out for a long time, the amount of fluid in a vessel decreases or increases, making it difficult to control of fluid amount in a culture vessel. Accordingly, stable culturing is difficult. Furthermore, when a culture is performed in these systems, it is usually required to increase a perfusion rate as much as possible in order to reduce a compositional change of a culture fluid; however, if a perfusion rate is increased more and more, the aforementioned control of fluid amount becomes difficult. Moreover, increasing the scale of culture results in increasing the perfusion rate. The same problem is produced.
As another method, Non Patent Literature 1 discloses a method of connecting a dialysis means to a rotor-type cell culture vessel. However, in such a culture, a specific cell culture vessel is required, which differs from the vessels of cell-culture apparatuses generally and widely used, and it is difficult to scale up a culture.